313P - Intrinsic subtypes in a cohort of early breast cancer patients

Background

Breast cancer is a heterogeneous disease with regard to diagnosis, therapy and survival. Complementary to the histopathological classifications of the tumours, molecular biological tests specify individualised therapy recommendations. Our aim was to classify tumours into intrinsic subtypes and to analyse the association of grouping with disease progression.

Methods

Intrinsic subtypes were determined from 1,070 tumours by mRNA expression profiling (PAM50 algorithm) from fresh tumour tissue or FFPE tissue in a prospective, multicenter cohort study (n=1,270; NCT 01592825). mRNA expression evaluation was performed either by nCounter®NanoString or GenChip™ HG U133 Plus 2.0 or BioMark™ Fluidigm. Endpoints were recurrence free interval (RFI) and overall survival (OS). Median follow-up time was 60.3 months. Survival analyses were done by Kaplan-Meier method and Cox model adjusting for age, nodal status, tumour size, and tumour differentiation.

Results

The PAM50 analysis resulted in 44.9% in Luminal A (n=480), 23.9% Luminal B (n=256), 14.4% HER2-enriched (n=154), and 16.8% in Basal-like (n=180). In the total cohort, 89.9% (95% CI 87.9-91.9) of patients were free of RFI event and 87.5% (95% CI 85.3-89.7) were alive at 5 years of observation. Of patients with a Luminal A tumour, 93% were free of RFI event (95% CI 88.1-97.9). The remaining patients had a substantially higher risk of RFI events: Luminal B, HR=3.3 (95% CI 1.78-6.01); HER2-enriched, HR=3.8 (95% CI 2.01-7.21); Basal-like, HR=4.7 (95% CI 2.53-8.7). In the Cox model, only tumour size (HR=2.5) and nodal status (HR=2.2) had a significant additional prognostic impact. Also with regard to OS, PAM50 subtypes, tumour size, and nodal status were the only significant prognostic factors.

Conclusions

Even after guideline-based therapy, the intrinsic subtypes still have prognostic significance. Nearly half the patients can be identified as Luminal A with an excellent course of disease, whilst patients with Luminal B, HER2-enriched, Basal-like still have a substatial risk of recurrence, requiring further improvement of therapy concepts.

Clinical trial identification

NCT01592825 (release date: 16.12.09).

Editorial acknowledgement

Legal entity responsible for the study

M. Vetter and E. Kantelhardt.

Funding

Wilhelm Roux Program of the Medical Faculty, Martin-Luther-University Halle-Wittenberg (grant number: FKZ 25/36) German Federal Ministry of Education and Research (grant number: Med FKZ 031A429).

Disclosure

C. Thomssen: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowiisen, Pfizer, Roche, Seagen, Vifor; Financial Interests, Personal, Financially compensated role: Forum Sanitas; Non-Financial Interests, Personal, Member: AGO Breast Committee, ASCO, DGGG (Germ Soc OB/GYN), DGS (Germ Soc Senology), DKG (Germ Cancer Soc), EORTC PathoBiomarker Group; Non-Financial Interests, Personal, Member of Board of Directors: AGO -B Breast Study Group; Non-Financial Interests, Personal, Officer, representing AGO-B: BIG; Non-Financial Interests, Personal, Invited Speaker: ESO; Non-Financial Interests, Personal, Steering Committee Member: ESMO. All other authors have declared no conflicts of interest.